A critical analysis of prognostic factors in North American patients with human T‐cell lymphotropic virus type‐1‐associated adult T‐cell leukemia/lymphoma

Abstract

BACKGROUND:To define the clinicopathologic and prognostic features of patients with human T-cell lymphotropic virus type-1 (HTLV-1)-associated adult T-cell leukemia/lymphoma (ATLL) in North America, standard criteria were used to identify patients with ATLL. METHODS: Statistical analyses used included descriptive statistics, Kaplan-Meir survival analysis, and recursive partitioning. RESULTS: Eighty-nine patients were identified between August 1992 and May 2007, including 37 (41.6%) males and 52 (58.4%) females with a median age of 50 years (range, 22-82 years). All but 6 patients had immigrated to the United States from the Caribbean, Latin America, or Africa. The acute subtype predominated (68.5%). The majority of patients received a combination-alkylator-based chemotherapy regimen in the front-line setting (72.6%). The most common regimen was cyclophosphamide, doxorubicin, vincristine, and prednisone at standard doses or attenuated and/or with methotrexate (CHOP-like), which produced an overall response rate of 64.1%. Despite initial responses to therapy, the median overall survival for all subtypes was 24 weeks (range, 0.9-315 weeks). Although the International Prognostic Index and Prognostic Index for peripheral T-cell lymphoma unspecified identified subsets of patients, these models were not completely predictive. A recursive partitioning analysis was performed on the data, which successfully identified 3 prognostic categories based on Eastern Cooperative Oncology Group performance status, stage, age, and calcium level at diagnosis. CONCLUSIONS: This series proposed a new prognostic model for patients with HTLV-1-associated ATLL and confirmed a poor outcome for these patients in North America. Cancer 2010;116:3438-46.

Epidemiology, clinical features, and outcome of HTLV-1–related ATLL in an area of prevalence in the United States

“…The median age of 52 at diagnosis was similar to previous US reports describing Afro-Caribbean patients and approximately a decade younger than Japanese patients. 6,7,12,20 However, in our patient population, lymphomatous ATLL was more common (49.2%) than acute ATLL (41%), which differed from patients presenting in New York City, where 68% of those encountered had acute ATLL, and Japan, where acute ATLL was also more common (56%, vs 22% lymphomatous). 7,12,20 Despite of variable ethnic populations encountered in New York, NY (a larger Caribbean/Hispanic group), Miami, FL (a large number of Haitians), and an unrelated ethnic group in Japan, a plausible explanation for such discrepancy could be differences in ATLL subclassification methods across centers.…”

“…6,7,12,20 However, in our patient population, lymphomatous ATLL was more common (49.2%) than acute ATLL (41%), which differed from patients presenting in New York City, where 68% of those encountered had acute ATLL, and Japan, where acute ATLL was also more common (56%, vs 22% lymphomatous). 7,12,20 Despite of variable ethnic populations encountered in New York, NY (a larger Caribbean/Hispanic group), Miami, FL (a large number of Haitians), and an unrelated ethnic group in Japan, a plausible explanation for such discrepancy could be differences in ATLL subclassification methods across centers. Shimoyama criteria excludes patients with $1% circulating ATLL cells as lymphomatous, so in the absence of a carefully designed prospective immunophenotypic and clonal analysis of peripheral blood, the distinction between lymphomatous ATLL with disseminated cells and other subtypes is often difficult to make.…”

“…7,20 Hypercalcemia and elevated LDH (.2N), which were independent factors associated with poorer survival in our previous meta-analysis, 16 were more frequent in acute ATLL cases (65% and 73%, respectively) than in large Japanese studies (up 50% and 60%, respectively). 8,12 A relative poorer survival has been reported in Afro-Caribbean patients in other US studies as compared with Japanese patients.…”

“…8,12 A relative poorer survival has been reported in Afro-Caribbean patients in other US studies as compared with Japanese patients. 7,20 While limited health care access to immigrants from poor resource settings could ultimately influence patient outcome, the above mentioned clinical findings suggest Afro-Caribbean patients encountered in the United States present with more aggressive ATLL. 16 When used as second-line treatment, response to AZT-IFN was low; however, 2 acute type patients treated within 3-6 weeks after chemotherapy initiation with kinetic failure had prolonged responses (5.9 years and 2.2 years) demonstrating some patients may benefit from AZT-IFN after failing chemotherapy.…”

“…6 ATLL occurs predominantly in adults between the sixth and seventh decades. 6,7 ATLL is classified into 4 clinical subtypes, namely acute, lymphomatous, chronic, and smoldering, as defined by Shimoyama criteria. 8 The most aggressive acute and lymphomatous forms are by far the most common, and patients frequently present with lymphadenopathy, hepatomegaly, splenomegaly, hypercalcemia, and involvement of the skin, lung, bones, and other organs.…”